Both stroke and dementia are conditions associated with significant disability, mortality, caregiver burden, and health care costs. White matter hyperintensities (WMH) and small cerebral infarcts seen on brain MRI among older adults are common, seem to represent subcortical vascular disease, and are associated with cognitive and functional decline. Preventing infarcts and WMH progression through identification of modifiable risk factors (such as potentially vitamin D deficiency) could reduce disability among older adults. Low serum 25-hydroxyvitamin D [25(OH)D] levels are associated with cardiovascular disease and its risk factors such as hypertension and diabetes. Limited emerging data suggest that vitamin D may be important for cognitive functioning and protective against neurovascular injury. In addition, low 25(OH)D levels have been linked to neurodegenerative disorders such as Alzheimer's. No prior study has evaluated the association of vitamin D with subclinical cerebrovascular disease measured by brain MRI imaging in a prospective fashion thus minimizing the concerns of reverse causation plagued by cross-sectional studies. To date, there has been little research in the area of vitamin D and cognitive decline. This grant proposes to measure serum 25(OH)D levels in 1878 participants (60% women, 50% black race/ethnicity) of the Atherosclerosis Risk in Communities (ARIC) Brain MRI longitudinal study using from stored blood drawn at visit 3 (1993-1994) to address the following 3 aims: (1) To determine the prospective association of 25(OH)D levels with WMH progression and incident subclinical infarcts measured by repeat brain MRI performed 10 years later (2004- 2006) (2) To determine whether lower 25(OH)D levels will be associated with cognitive decline over 14 years of followup in 3 key cognitive domains (memory, language, word processing) (3) To determine whether 25(OH)D deficiency predicts incident clinical stroke/TIA over 10-15 years of followup. A subset will repeat cognitive testing and undergo a third Brain MRI in 2011-2013. Vitamin D deficiency is easy to screen for, although not yet widely accepted in clinical practice. Furthermore vitamin D deficiency is easy and affordable to treat with supplementation. Thus, if an association of 25(OH)D deficiency with stroke and cognitive decline is found and confirmed in subsequent clinical trials, this could have important implications for health policy and patient care with regard to screening and treatment for primary prevention of cerebrovascular disease. PUBLIC HEALTH RELEVANCE: Vitamin D deficiency is common in the United States and has been associated with increased cardiovascular risk. Recent preliminary data suggests that adequate levels of vitamin D may be also important for preventing stroke, cognitive decline, and dementia, but this has been less well studied. We plan to measure vitamin D levels from stored blood from participants of the Atherosclerosis Risk In Communities (ARIC) Brain Magnetic Resonance Imaging (MRI) study who already completed 2 brain MRI scans taken 10 years apart and 4 sessions of comprehensive cognitive testing spanning 14 years to evaluate the role of vitamin D in brain aging.